The genes encoded by the major histocompatibility complex (MHC) of mammals have been shown to be involved in a number of developmental pathways including cleft palate formation, the action of hormones on cells, and the levels of cellular cyclic AMP in mice. Some studies also indicate that cellular adhesion, which may be involved in the proper homing of cells during organogenesis, is under the influence MHC products. Recently, it has been shown that histocompatibility gene products are crucial for the maturation and function of the immune system. We have developed a fetal organ culture system to study the development of murine thymus derived immunocompetent cells (T-cells) and murine bone marrow derived immunocompetent cells (B-cells) in a closed system where cell yields during differentiation can be easily monitored. Fusion between allogeneic murine fetal thymus lobes in organ culture results in a profound loss in the yield of immunocompetent cells as compared with syngeneic controls. This loss occurs without detectable immune response. In fact, the cells which are recovered from these fusions are specifically tolerant in mixed lymphocyte culture analysis. Studies to determine the ability of cells in allogeneic fusions to divide implies that these cells lack the proper microenvironment to begin division and differentiation. We intend to determine (1) the contribution of epithelial cells to T-cell maturation, (2) the exact timing of self-tolerance induction and immunocompetent cell growth by altering the time of fetal thymus lobe fusion, (3) the histocompatibility gene locus responsible for muturation of T-progenitor cells.